Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD.

OBJECTIVE: Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4(+) T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process in vivo remains unknown. The aim of the present study was to identify the CD4(+) T cell subsets involved in the process of osteoclastogenesis in vivo, as well as their mechanism of action. DESIGN: CD4(+) T cells were studied in IL10-/- mice and Rag1-/- mice adoptively transferred with naive CD4(+)CD45RB(high) T cells, representing two well-characterised animal models of IBD and in patients with Crohn's disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors. RESULTS: In mice, we identified bone marrow (BM) CD4(+) T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α(+) cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α(+) cells was also detected in patients with Crohn's disease. CONCLUSIONS: Our results highlight the osteoclastogenic function of the Th17 TNF-α(+) cells that contribute to bone loss in vivo in IBD.

The on-call crisis: a statewide assessment of the costs of providing on-call specialist coverage.

STUDY OBJECTIVE: A recent change in the delivery of emergency care is a growing reluctance of specialists to take call. The objective of this study is to survey Oregon hospitals about the prevalence and magnitude of stipends for taking emergency call and to assess the ways in which hospitals are limiting services. METHODS: This was a cross-sectional, standardized survey of chief executive officers from all hospitals with emergency departments in Oregon (N=56). This e-mail-based survey asked about payments made to specialists to take call and examined changes in hospitals' trauma designation and ability to provide continuous coverage for certain specialties. RESULTS: We received responses from 54 of 56 hospitals, representing a 96% response rate (100% of trauma centers). Twenty-three of 54 (43%) Oregon hospitals pay a stipend to at least 1 specialty, and 17 (31%) hospitals guarantee pay for uninsured patients treated on call. Stipends ranged from $300 per month to more than $3,000 per night, with a median stipend of $1,000 per night to take call. Trauma surgeons, neurosurgeons, and orthopedists were the specialists most likely to receive stipends. Seven of 54 (13%) hospitals have had their trauma designation affected by on-call issues. Twenty-six hospitals (48%) have lost the ability to provide continuous coverage for at least 1 specialty. CONCLUSION: Problems with on-call coverage are prevalent in Oregon and affect hospital financing and delivery of services. A continuation of the current situation could degrade the effectiveness of the trauma system and adversely affect the quality of emergency care.